Interferon - a product of macrophages and B lymphocytes - has been found to exert effects at the level of the central nervous system in humans and in laboratory animals. Clinical trials have revealed severe psychiatric complications following the administration of interferon that closely resemble those of AIDS related dementia. These symptoms include depression, paranoia as well as suicidal potential which usually resolve once therapy is stopped. An acid labile form of interferon has also been found at high levels in AIDS patients, many of whom are found amongst the drug abuse population. Using animal models, it has been found that alpha interferon is able to attenuate the behavioral manifestations of naloxone induced withdrawal from morphine. The proposed studies have been designed to further characterize and to extend the various reports that interferon has central nervous system effects, some of which can modulate the intensity of naloxone-induced withdrawal in morphine-dependent rats. The withdrawal model will be used in order to identify brain sites where interferon is active as well as to identify specific neurotransmitters that may be altered by interferon. In addition, behaviors that comprise the withdrawal response will be thoroughly evaluated. These studies have wide-ranging implications in both the basic science and clinical settings. A number of immune system products are now known to be active at the level of the brain and/or pituitary gland and so these studies will further our understanding of bidirectional pathways that link the brain with the immune system. They may also reveal that measures of immunologic status may have predictive value in determining the severity of withdrawal symptoms. A multidisciplinary approach to studying this question is proposed and includes individuals highly experienced in working with all of the varied aspects of this study.